1. Field of the Invention
This invention relates to a stabilized pharmaceutical composition prepared by admixing a low-melting fat- or oil-like substance with disodium adenosine triphosphate (hereinafter sometimes referred to briefly as "ATP-2Na"), which is useful, for example, in alleviating or treating cerebrovascular disorder, cardiac failure and asthenopia, and to a method of producing such composition.
2. Description of the Prior Art
Since the discovery by Fiske and Lohmann et al. (1929) of adenosine triphosphate (hereinafter sometimes referred to briefly as "ATP") occurring in muscular tissue infusions, the role of disodium adenosine triphosphate in living organisms has been elucidated step by step by a number of researchers. As a representative of the compounds having the so-called energy rich phosphate bond, ATP is found everywhere in living organisms. The energy required in living organisms is supplied solely by ATP. On the other hand, the clinical use of ATP-2Na as a therapeutic agent has become fairly popular and its efficacy has been established in certain diseases.
While ATP-2Na is useful as a therapeutic agent for various purposes, as mentioned above, it has drawbacks. Thus, in the solid form, it is unstable under high temperature and/or high humidity conditions and, in the form of an aqueous solution or suspension, its stability decreases with the decreasing pH value. Therefore, preparations or dosage forms containing it, particularly tablets, have poor stability as far as ATP-2Na is concerned. The content of the active ingredient in said preparations decreases with the lapse of time and coloration occurs before long.
In some pharmaceutical compositions containing other ingredients, ATP-2Na strongly interacts with said other ingredients, leading to still more decreased stability. Furthermore, in the case of tablets, crystals are distorted due to the pressure, friction, heat and other effects applied or produced in the step of molding under pressure and as a result, the fall in content with the lapse of time is accelerated in many instances.
While, as mentioned above, ATP-2Na is under research and development for use as an agent for treating or alleviating various diseases, the stability problem in producing preparations containing it has not been solved to a satisfactory extent as yet. In particular, the art has not yet known any technology that could prevent such decomposition of the active ingredient ATP-2Na with the lapse of time as mentioned above and thereby improve the stability of ATP-2Na preparations produced in the form of solid preparations such as tablets and therefore could be put to practical use. As a result, the conventional ATP-2Na preparations are disadvantageous without exception particularly in that their quality can be guaranteed only for a short period of time and that they must be stored in a cool place.
Accordingly, it is an object of the invention to provide a stabilized ATP-2Na preparation. Another object is to provide a means of stabilizing ATP-2Na which is quite practicable from the cost viewpoint as well and which is other than those prior art means that often lead to increases in drug preparation cost, such as extra charge of drugs, extreme reduction of water content, etc. A further object of the invention is to provide such means of stabilizing ATP-2Na preparations to thereby prolong the period over which the quality of products can be guaranteed, make the products storable under less strict conditions and heighten the commercial value of the products.
Under the circumstances such as mentioned above, the present inventors made various attempts to stabilize ATP-2Na-containing preparations by addition of bases, clathration with cyclodextrins and the like, and addition of antioxidants, among others, but failed to find out any stabilizing effect of satisfactorily practical significance. As a result of further investigations, however, the present inventors unexpectedly found that when a low-melting fat- or oil-like substance is incorporated into ATP-2Na preparations, the decomposition of ATP-2Na can be prevented to a remarkable extent and stable preparations can be obtained. As a result of continued investigations based on this finding, they have now completed the present invention.